Evaluation of 18F-DPA-714 PET-MRI for Preoperative Localization in Drug-Resistant Partial Epilepsy Candidates for Surgical Resection

The primary objective of this study is to evaluate the contribution of **18F-DPA-714 PET imaging** in accurately locating the seizure zone in patients aged 12 and over with drug-resistant partial epilepsy who are candidates for surgical intervention during their phase 2 work-up. This is clinically relevant as precise localization of the epileptic focus is crucial for the success of surgical resection, potentially improving patient outcomes by reducing seizure frequency or achieving seizure freedom.

Secondary objectives include:

• Evaluate the feasibility and tolerance of the entire procedure.
• Evaluate the efficacy at 1 year of surgical intervention in the event of removal of the focus designated by imaging.
• Study the influence of "epilepsy type" (location, etiology) on imaging results.
• Study the factors associated with surgical failure in relation to imaging data.
• Compare the volume resected in surgery with the volume defined on the basis of imaging results.
• Study the imaging results of patients rejected after SEEG.
• Compare the topography of the data from the 18F-DPA-714 PET imaging with those of MRI imaging (diffusion tensor and T1 and T2 morphological MRI).
• Assess the impact of the epileptic focus on remote brain function (resting-state functional MRI).

The clinical trial involves **patients with drug-resistant epilepsy** who are candidates for surgery requiring stereoelectroencephalography (SEEG), as well as healthy volunteers. The study population includes both male and female participants. Patients must be aged 12 years and older, while healthy volunteers are required to be between 18 and 55 years of age. The trial does not involve a vulnerable population. Participants were selected based on specific criteria, including the persistence of epilepsy after two types of well-conducted treatment for patients, and the absence of chronic or progressive general pathology for healthy volunteers. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the contribution of **18F-DPA-714** PET imaging in locating the seizure zone in patients aged 12 and over with drug-resistant partial epilepsy who are candidates for surgery. This study is a **randomized, double-blind, controlled** trial, conducted in Phase 3, and is expected to conclude by November 2025. The trial involves the administration of **18F-DPA-714** via **intravenous injection**. The primary endpoint is the percentage of subjects in whom the epileptogenic volume defined by SEEG, performed according to the electrode implantation plan determined with multimodal PET-MRI imaging, will have been correctly modified compared with the plan determined without multimodal imaging data.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, epilepsy status, and previous surgical assessments. Follow-up visits will be scheduled to monitor the imaging results and any adverse events. The end-of-study visit will evaluate the overall outcomes, including the number of seizures one year post-surgery and the relationship between the epileptic focus and remote brain function. The expected length of participant involvement is from the recruitment start date in November 2018 until the estimated end date in November 2025. Conditions that may lead to early termination from the study include non-compliance with the protocol, withdrawal of consent, or adverse events that compromise participant safety.

The clinical trial involves the use of the experimental medication **18F-DPA-714**, which is administered in the form of an **injection**. The active substance in this medication is **N,N-diethyl-2-(2-(4-(2[(18)F]-fluoroethoxy)phenyl)5,7dimethylpyrazolo[1,5a]pyrimidin-3-yl)acetamide**. This compound is of chemical origin and is utilized for its potential in improving the preoperative localization of the epileptic focus in patients with drug-resistant partial epilepsy. The administration route for **18F-DPA-714** is **intravenous**, ensuring direct delivery into the bloodstream. The frequency and dosage of administration are determined based on the specific requirements of the trial protocol, although specific dosing schedules are not detailed in the provided data.

In this study, **18F-DPA-714** is the primary investigational product, and no additional non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are mentioned. The trial aims to evaluate the contribution of **18F-DPA-714** PET imaging in locating the seizure zone in patients aged 12 and over who are candidates for surgery. Participant compliance with the administration protocol is monitored throughout the trial to ensure adherence to the dosing schedule and to assess the efficacy and safety of the investigational product. The trial is conducted under the auspices of the **INST NATIONAL SANTE ET RECHERCHE MEDICALE**, which is responsible for the development and oversight of the investigational product.

Efficacy in this clinical trial will be assessed primarily by evaluating the percentage of subjects in whom the **epileptogenic volume** defined by SEEG (stereoelectroencephalography) is correctly modified when using the electrode implantation plan determined with multimodal PET-MRI imaging, compared to the plan determined without such imaging data. This primary endpoint aims to determine the contribution of 18F-DPA-714 PET imaging in accurately locating the seizure zone in patients with drug-resistant partial epilepsy who are candidates for surgery.

Secondary endpoints include the collection and analysis of adverse events and their causal relationship to the procedure, the number of subjects who benefited from the procedure according to the protocol, and the number of seizures in patients one year post-surgery, classified by the ILAE classification. Additional secondary endpoints involve the study of imaging results in subgroups of patients based on epilepsy type, imaging data in patients not cured by surgery, and those rejected after SEEG. The trial will also examine the topography of PET imaging data compared to MRI data and the relationship between the epileptic focus and remote brain function.